ENST00000462876.5:n.1007-2570A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000462876.5(CAV2):​n.1007-2570A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,170 control chromosomes in the GnomAD database, including 967 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.10 ( 967 hom., cov: 32)

Consequence

CAV2
ENST00000462876.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.938

Publications

7 publications found
Variant links:
Genes affected
CAV2 (HGNC:1528): (caveolin 2) The protein encoded by this gene is a major component of the inner surface of caveolae, small invaginations of the plasma membrane, and is involved in essential cellular functions, including signal transduction, lipid metabolism, cellular growth control and apoptosis. This protein may function as a tumor suppressor. This gene and related family member (CAV1) are located next to each other on chromosome 7, and express colocalizing proteins that form a stable hetero-oligomeric complex. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene. Additional isoforms resulting from the use of alternate in-frame translation initiation codons have also been described, and shown to have preferential localization in the cell (PMID:11238462). [provided by RefSeq, May 2011]
CAV2 Gene-Disease associations (from GenCC):
  • amyotrophic lateral sclerosis
    Inheritance: AD Classification: LIMITED Submitted by: ClinGen

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CAV2-DTNR_188009.1 linkn.163+4155T>C intron_variant Intron 1 of 3
CAV2-DTNR_188010.1 linkn.163+4155T>C intron_variant Intron 1 of 3
CAV2-DTNR_188011.1 linkn.163+4155T>C intron_variant Intron 1 of 4
CAV2-DTNR_188012.1 linkn.163+4155T>C intron_variant Intron 1 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CAV2ENST00000462876.5 linkn.1007-2570A>G intron_variant Intron 8 of 13 1
CAV2ENST00000467035.5 linkn.753-2570A>G intron_variant Intron 6 of 8 1
CAV2ENST00000472470.5 linkn.407-2570A>G intron_variant Intron 3 of 5 1

Frequencies

GnomAD3 genomes
AF:
0.102
AC:
15460
AN:
152052
Hom.:
961
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.174
Gnomad AMI
AF:
0.131
Gnomad AMR
AF:
0.0679
Gnomad ASJ
AF:
0.0900
Gnomad EAS
AF:
0.000578
Gnomad SAS
AF:
0.0215
Gnomad FIN
AF:
0.0650
Gnomad MID
AF:
0.0696
Gnomad NFE
AF:
0.0844
Gnomad OTH
AF:
0.103
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.102
AC:
15488
AN:
152170
Hom.:
967
Cov.:
32
AF XY:
0.0976
AC XY:
7263
AN XY:
74420
show subpopulations
African (AFR)
AF:
0.175
AC:
7253
AN:
41486
American (AMR)
AF:
0.0677
AC:
1035
AN:
15278
Ashkenazi Jewish (ASJ)
AF:
0.0900
AC:
312
AN:
3468
East Asian (EAS)
AF:
0.000580
AC:
3
AN:
5176
South Asian (SAS)
AF:
0.0211
AC:
102
AN:
4830
European-Finnish (FIN)
AF:
0.0650
AC:
690
AN:
10614
Middle Eastern (MID)
AF:
0.0646
AC:
19
AN:
294
European-Non Finnish (NFE)
AF:
0.0844
AC:
5740
AN:
68014
Other (OTH)
AF:
0.102
AC:
215
AN:
2100
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
710
1421
2131
2842
3552
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
156
312
468
624
780
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0948
Hom.:
2243
Bravo
AF:
0.108
Asia WGS
AF:
0.0160
AC:
57
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.50
CADD
Benign
13
DANN
Benign
0.80
PhyloP100
0.94

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs17138756; hg19: chr7-116135253; API